Not provided
| ID | Type | Description | Link |
|---|---|---|---|
| 2006-004893-29 | EudraCT Number | ||
| HMR1726D-2004 | Other Identifier | HMR |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
The primary objective was to estimate the tolerability and safety of 2 doses of Teriflunomide administered once daily for 24 weeks, compared to placebo, in patients with multiple sclerosis [MS] with relapses who were on a stable dose of Glatiramer Acetate [GA].
The secondary objectives were:
The duration of the study period for a participant was approximatively 44 weeks broken down as follows:
'*' Participants successfully completing the week 24 visit were offered the opportunity to enter the optional long-term extension study LTS6047 - NCT00811395.
Not provided
Not provided
Not provided
Not provided
| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Placebo + GA | Placebo Comparator | Placebo (for teriflunomide) once daily concomitantly with glatiramer acetate (GA) for 24 weeks |
|
| Teriflunomide 7 mg + GA | Experimental | Teriflunomide 7 mg once daily concomitantly with glatiramer acetate (GA) for 24 weeks |
|
| Teriflunomide 14 mg + GA | Experimental | Teriflunomide 14 mg once daily concomitantly with glatiramer acetate (GA) for 24 weeks |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Teriflunomide | Drug | Film-coated tablet Oral administration |
|
| Measure | Description | Time Frame |
|---|---|---|
| Overview of Adverse Events (AE] | AE are any unfavorable and unintended sign, symptom, syndrome, or illness observed by the investigator or reported by the participant during the study. | from first study drug intake up to 112 days after last intake or up to the first intake in the extension study LTS6047, whichever occured first (40 weeks max) |
| Overview of AE With Potential Risk of Occurrence | AE with potential risk of occurrence were defined as follows:
| from first study drug intake up to 112 days after last intake or up to the first intake in the extension study LTS6047, whichever occured first (40 weeks max) |
| Liver Function: Number of Participants With Potentially Clinically Significant Abnormalities (PCSA) | PCSA values are abnormal values considered medically important by the Sponsor according to predefined criteria based on literature review. Hepatic parameters thresholds were defined as follows:
| from first study drug intake up to 112 days after last intake or up to the first intake in the extension study LTS6047, whichever occured first (40 weeks max) |
| Measure | Description | Time Frame |
|---|---|---|
| Cerebral Magnetic Resonance Imaging [MRI] Assessment: Change From Baseline in Total Lesion Volume (Burden of Disease) | Total lesion volume is the sum of the total volume of all T2-lesions and the total volume all T1-hypointense post-gadolinium lesions measured through T2/proton density scan analysis and gadolinium-enhanced T1 scan analysis. Least-square means were estimated using a Mixed-effect model with repeated measures [MMRM] on cubic root transformed volume data (treatment group, region of enrollment, visit, treatment-by-visit interaction, baseline value (cubic root transformed), and baseline-by-visit interaction as factors). |
Not provided
Inclusion Criteria:
Exclusion Criteria:
The above information is not intended to contain all considerations relevant to a patient's potential participation in a clinical trial.
Not provided
Not provided
Not provided
Not provided
Not provided
| Name | Affiliation | Role |
|---|---|---|
| ICD CSD | Sanofi | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Sanofi-Aventis Administrative Office | Bridgewater | New Jersey | 08807 | United States | ||
| Sanofi-Aventis Administrative Office |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 28607708 | Derived | Freedman MS, Wolinsky JS, Truffinet P, Comi G, Kappos L, Miller AE, Olsson TP, Benamor M, Chambers S, O'Connor PW. A randomized trial of teriflunomide added to glatiramer acetate in relapsing multiple sclerosis. Mult Scler J Exp Transl Clin. 2015 Dec 7;1:2055217315618687. doi: 10.1177/2055217315618687. eCollection 2015 Jan-Dec. |
Not provided
Not provided
Randomization was stratified by country.
Assignment to groups was done centrally using an Interactive Voice Response System (IVRS] in a 1:1:1 ratio after confirmation of the selection criteria.
123 participants were randomized.
The recruitment initiated in April 2007 was completed in December 2008.
A total of 148 patients were screened at 24 sites in 6 countries.
Not provided
| ID | Title | Description |
|---|---|---|
| FG000 | Placebo + GA | Placebo (for teriflunomide) once daily concomitantly with Glatiramer Acetate [GA] for 24 weeks |
| FG001 | Teriflunomide 7 mg + GA | Teriflunomide 7 mg once daily concomitantly with Glatiramer Acetate [GA] for 24 weeks |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
|
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Placebo (for teriflunomide) | Drug | Film-coated tablet Oral administration |
|
| Glatiramer Acetate (GA) | Drug | Solution in prefilled syringe for subcutaneous injection |
|
|
| baseline (before randomization) and 24 weeks |
| Cerebral MRI Assessment: Number of Gd-enhancing T1-lesions Per Scan (Poisson Regression Estimates) | Number of Gd-enhancing T1-lesions per scan is obtained from the total number of Gd-enhancing T1-lesions observed during the study divided by the total number of scans performed during the study. To account for the different number of scans among participants, a Poisson regression model with robust error variance was used (total number of Gd-enhancing T1-lesions as response variable; log-transformed number of scans as "offset" variable; treatment group, region of enrollment and baseline number of Gd-enhancing T1-lesions as covariates). | 24 weeks |
| Cerebral MRI Assessment: Volume of Gd-enhancing T1-lesions Per Scan | Total volume of Gd-enhancing T1-lesions per scan is obtained from the sum of the volumes of Gd-enhancing T1-lesions observed during the study divided by the total number of scans performed during the study. | 24 weeks |
| Annualized Relapse Rate [ARR]: Poisson Regression Estimates | ARR is obtained from the total number of confirmed relapses that occured during the treatment period divided by the sum of the treatment durations. Each episode of relapse - appearance, or worsening of a clinical symptom that was stable for at least 30 days, that persisted for a minimum of 24 hours in the absence of fever - was to be confirmed by an increase in Expanded Disability Status Scale [EDSS] score or Functional System scores. To account for the different treatment durations among participants, a Poisson regression model with robust error variance was used (total number of confirmed relapses as response variable; log-transformed treatment duration as "offset" variable; treatment group and region of enrollment as covariates). | 24 weeks |
| Pharmacokinetic [PK]: Teriflunomide Plasma Concentration | Plasma concentrations of teriflunomide were measured using validated liquid chromatography-tandem mass spectrometry methods. | 24 weeks |
| Vienna |
| Austria |
| Sanofi-Aventis Administrative Office | Laval | Canada |
| Sanofi-Aventis Administrative Office | Berlin | Germany |
| Sanofi-Aventis Administrative Office | Milan | Italy |
| Sanofi-Aventis Administrative Office | Guildford | United Kingdom |
| FG002 | Teriflunomide 14 mg + GA | Teriflunomide 14 mg once daily concomitantly with Glatiramer Acetate [GA] for 24 weeks |
| Treated |
|
| COMPLETED |
|
| NOT COMPLETED |
|
|
Not provided
| ID | Title | Description |
|---|---|---|
| BG000 | Placebo + GA | Placebo (for Teriflunomide) once daily concomitantly with glatiramer acetate [GA] for 24 weeks |
| BG001 | Teriflunomide 7 mg + GA | Teriflunomide 7 mg once daily concomitantly with glatiramer acetate [GA] for 24 weeks |
| BG002 | Teriflunomide 14 mg + GA | Teriflunomide 14 mg once daily concomitantly with glatiramer acetate [GA] for 24 weeks |
| BG003 | Total | Total of all reporting groups |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age Continuous | Mean | Standard Deviation | years |
| |||||||||||||||
| Sex: Female, Male | Count of Participants | Participants |
| ||||||||||||||||
| Region of Enrollment | Europe: Austria, Germany, Italy and United Kingdom North America: Canada and United States | Number | participants |
| |||||||||||||||
| Time since first diagnosis of Multiple Sclerosis [MS] | Mean | Standard Deviation | years |
| |||||||||||||||
| Number of MS relapses | Median | Full Range | MS relapses |
| |||||||||||||||
| Time since most recent MS relapse onset | Mean | Standard Deviation | months |
| |||||||||||||||
| MS subtype | Number | participants |
| ||||||||||||||||
| Baseline Expanded Disability Status Scale [EDSS] score | EDSS is an ordinal scale in half-point increments that qualifies disability in patients with MS. It consists of 8 ordinal rating scales assessing seven functional systems (visual, brainstem, pyramidal, cerebellar, sensory, bowel/bladder and cerebral) as well as ambulation. EDSS total score ranges from 0 (normal neurological examination) to 10 (death due to MS). | Mean | Standard Deviation | units on a scale |
|
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Overview of Adverse Events (AE] | AE are any unfavorable and unintended sign, symptom, syndrome, or illness observed by the investigator or reported by the participant during the study. | All randomized and treated participants; Participants were included in the treatment group according to the drug actually received. | Posted | Number | participants | from first study drug intake up to 112 days after last intake or up to the first intake in the extension study LTS6047, whichever occured first (40 weeks max) |
|
|
| |||||||||||||||||||||||||||||||||||
| Primary | Overview of AE With Potential Risk of Occurrence | AE with potential risk of occurrence were defined as follows:
| All randomized and treated participants; Participants were included in the treatment group according to the drug actually received. | Posted | Number | participants | from first study drug intake up to 112 days after last intake or up to the first intake in the extension study LTS6047, whichever occured first (40 weeks max) |
| |||||||||||||||||||||||||||||||||||||
| Primary | Liver Function: Number of Participants With Potentially Clinically Significant Abnormalities (PCSA) | PCSA values are abnormal values considered medically important by the Sponsor according to predefined criteria based on literature review. Hepatic parameters thresholds were defined as follows:
| All randomized and treated participants; Participants were included in the treatment group according to the drug actually received. | Posted | Number | participants | from first study drug intake up to 112 days after last intake or up to the first intake in the extension study LTS6047, whichever occured first (40 weeks max) |
| |||||||||||||||||||||||||||||||||||||
| Secondary | Cerebral Magnetic Resonance Imaging [MRI] Assessment: Change From Baseline in Total Lesion Volume (Burden of Disease) | Total lesion volume is the sum of the total volume of all T2-lesions and the total volume all T1-hypointense post-gadolinium lesions measured through T2/proton density scan analysis and gadolinium-enhanced T1 scan analysis. Least-square means were estimated using a Mixed-effect model with repeated measures [MMRM] on cubic root transformed volume data (treatment group, region of enrollment, visit, treatment-by-visit interaction, baseline value (cubic root transformed), and baseline-by-visit interaction as factors). | All randomized and treated participants; Participants were included in the treatment group according to the drug actually received. | Posted | Least Squares Mean | Standard Error | mililiters (mL) | baseline (before randomization) and 24 weeks |
| ||||||||||||||||||||||||||||||||||||
| Secondary | Cerebral MRI Assessment: Number of Gd-enhancing T1-lesions Per Scan (Poisson Regression Estimates) | Number of Gd-enhancing T1-lesions per scan is obtained from the total number of Gd-enhancing T1-lesions observed during the study divided by the total number of scans performed during the study. To account for the different number of scans among participants, a Poisson regression model with robust error variance was used (total number of Gd-enhancing T1-lesions as response variable; log-transformed number of scans as "offset" variable; treatment group, region of enrollment and baseline number of Gd-enhancing T1-lesions as covariates). | All randomized and treated participants; Participants were included in the treatment group according to the drug actually received. | Posted | Number | 95% Confidence Interval | lesions per scan | 24 weeks |
| ||||||||||||||||||||||||||||||||||||
| Secondary | Cerebral MRI Assessment: Volume of Gd-enhancing T1-lesions Per Scan | Total volume of Gd-enhancing T1-lesions per scan is obtained from the sum of the volumes of Gd-enhancing T1-lesions observed during the study divided by the total number of scans performed during the study. | All randomized and treated participants; Participants were included in the treatment group according to the drug actually received. | Posted | Number | mililiters per scan | 24 weeks |
|
| ||||||||||||||||||||||||||||||||||||
| Secondary | Annualized Relapse Rate [ARR]: Poisson Regression Estimates | ARR is obtained from the total number of confirmed relapses that occured during the treatment period divided by the sum of the treatment durations. Each episode of relapse - appearance, or worsening of a clinical symptom that was stable for at least 30 days, that persisted for a minimum of 24 hours in the absence of fever - was to be confirmed by an increase in Expanded Disability Status Scale [EDSS] score or Functional System scores. To account for the different treatment durations among participants, a Poisson regression model with robust error variance was used (total number of confirmed relapses as response variable; log-transformed treatment duration as "offset" variable; treatment group and region of enrollment as covariates). | All randomized and treated participants; Participants were included in the treatment group according to the drug actually received. | Posted | Number | 95% Confidence Interval | relapses per year | 24 weeks |
| ||||||||||||||||||||||||||||||||||||
| Secondary | Pharmacokinetic [PK]: Teriflunomide Plasma Concentration | Plasma concentrations of teriflunomide were measured using validated liquid chromatography-tandem mass spectrometry methods. | All randomized and treated participants who had at least one PK sample. Participants were included in the treatment group according to the drug actually received. | Posted | Mean | Standard Deviation | micrograms/mililiter (μg/mL) | 24 weeks |
|
|
All Adverse Events (AE) were collected regardless of seriousness or relationship to the drug, spanning from signature of the Informed Consent Form up to the last visit.
The analysis was performed on the exposed population and included all AE that developed or worsened from first study drug intake up to 112 days after last study drug intake or up to the first study drug intake in the extension study LTS6047, whichever occured first (40 weeks max)
Not provided
| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Placebo + GA | Placebo (for Teriflunomide) once daily concomitantly with glatiramer acetate [GA] for 24 weeks | 3 | 41 | 20 | 41 | ||
| EG001 | Teriflunomide 7 mg + GA | Teriflunomide 7 mg once daily concomitantly with glatiramer acetate [GA] for 24 weeks | 3 | 42 | 20 | 42 | ||
| EG002 | Teriflunomide 14 mg + GA | Teriflunomide 14 mg once daily concomitantly with glatiramer acetate [GA] for 24 weeks | 1 | 40 | 25 | 40 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Abscess | Infections and infestations | MedDRA 11.1 | Non-systematic Assessment |
| |
| Suicidal ideation | Psychiatric disorders | MedDRA 11.1 | Non-systematic Assessment |
| |
| Cerebral ischaemia | Nervous system disorders | MedDRA 11.1 | Non-systematic Assessment |
| |
| Epilepsy | Nervous system disorders | MedDRA 11.1 | Non-systematic Assessment |
| |
| Interstitial lung disease | Respiratory, thoracic and mediastinal disorders | MedDRA 11.1 | Non-systematic Assessment |
| |
| Alanine aminotransferase increased | Investigations | MedDRA 11.1 | Non-systematic Assessment |
| |
| Hepatic enzyme increased | Investigations | MedDRA 11.1 | Non-systematic Assessment |
| |
| Facial bones fracture | Injury, poisoning and procedural complications | MedDRA 11.1 | Non-systematic Assessment |
|
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Gastroenteritis | Infections and infestations | MedDRA 11.1 | Non-systematic Assessment |
| |
| Nasopharyngitis | Infections and infestations | MedDRA 11.1 | Non-systematic Assessment |
| |
| Upper respiratory tract infection | Infections and infestations | MedDRA 11.1 | Non-systematic Assessment |
| |
| Urinary tract infection | Infections and infestations | MedDRA 11.1 | Non-systematic Assessment |
| |
| Dizziness | Nervous system disorders | MedDRA 11.1 | Non-systematic Assessment |
| |
| Headache | Nervous system disorders | MedDRA 11.1 | Non-systematic Assessment |
| |
| Paraesthesia | Nervous system disorders | MedDRA 11.1 | Non-systematic Assessment |
| |
| Constipation | Gastrointestinal disorders | MedDRA 11.1 | Non-systematic Assessment |
| |
| Diarrhoea | Gastrointestinal disorders | MedDRA 11.1 | Non-systematic Assessment |
| |
| Nausea | Gastrointestinal disorders | MedDRA 11.1 | Non-systematic Assessment |
| |
| Alopecia | Skin and subcutaneous tissue disorders | MedDRA 11.1 | Non-systematic Assessment |
| |
| Rash | Skin and subcutaneous tissue disorders | MedDRA 11.1 | Non-systematic Assessment |
| |
| Fatigue | General disorders | MedDRA 11.1 | Non-systematic Assessment |
|
The investigator can publish only the results of the work performed pursuant to this protocol. Prior to publication, the investigator provides the sponsor with the manuscript for review and comment at least 45 days in advance of its submission for publication.
The sponsor can require the investigator to withhold publication an additional 90 days to allow for filing a patent application or taking such other measures as sponsor deems appropriate to establish and preserve its proprietary rights.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Trial Transparency Team | sanofi-aventis | Contact_US@sanofi.com |
| ID | Term |
|---|---|
| D009103 | Multiple Sclerosis |
| D012008 | Recurrence |
| ID | Term |
|---|---|
| D020278 | Demyelinating Autoimmune Diseases, CNS |
| D020274 | Autoimmune Diseases of the Nervous System |
| D009422 | Nervous System Diseases |
| D003711 | Demyelinating Diseases |
| D001327 | Autoimmune Diseases |
| D007154 | Immune System Diseases |
| D020969 | Disease Attributes |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
Not provided
Not provided
| ID | Term |
|---|---|
| C527525 | teriflunomide |
| D000068717 | Glatiramer Acetate |
| ID | Term |
|---|---|
| D010455 | Peptides |
| D000602 | Amino Acids, Peptides, and Proteins |
Not provided
Not provided
| Male |
|
| North America |
|
| Within the past 2 years |
|
| Secondary Progressive |
|
| Progressive Relapsing |
|
| Title | Measurements |
|---|---|
|
| - AE leading to death |
|
| - AE leading to study drug discontinuation |
|
| Units | Counts |
|---|---|
| Participants |
|
|
|
|
|
|
|
|
|
|
Teriflunomide 14 mg once daily concomitantly with glatiramer acetate [GA] for 24 weeks |
|
|
|